| Purpose:Our study aimed to evaluate deep molecular response(DMR) and its impact on prognosis in patients with chronic myeloid leukemia in chronic phase (CML-CP) at specific intervals of treatment with imatinib(IM), determine the incidence of stable DMR and predictive factors.Methods:Patients with newly diagnosed CML-CP who received IM in the department of hematology in our hospital were retrospectively analyzed. MR4(BCR-ABL≤0.01%IS,≥4-logs reductions in BCR-ABL transcript levels) rates at6,12,18and24months after commencing IM were assessed. Overall survival(OS), progression-free survival (PFS) were analyzed in patients achieving MR4at specific time points mentioned above. The interval time from treatment to MR4was analyzed as well. Several factors were examined for association with Stable MR4(BCR-ABL remained≤0.01%IS for a continuous period of2years):sex, age, interval time from diagnosis to treatment, standard dose IM treatment, white blood cell(WBC) count and platelet count at baseline, the BCR-ABL level at3months,MR4at6,12,18,24months. Results:237patients with newly diagnosed CML-CP were enrolled.113(47.7%) patients achieved MR4at the time of last follow-up. The overall incidence of MR4was51.1%. The incidences of MR4at6,12,18,24months after commencing IM were8.2%,25.8%,31.3%,35.4%, respectively. In patients accepted IM within6months of diagnosis, the incidences of MR4at6,12,18,24months were13.5%,28.3%,34.4%,38.9%, in which the incidences of MR4at12,18,24months were significantly better than those in patients with an IM interval greater than6months(12months:28.3%vs11.8%, p=0.043,18months:34.4%vs14.7%, p=0.023,24months:38.9%vs16.7%, p=0.019). Reduced dose IM was not associated with the incidence of MR4at specific intervals of treatment. There was significant difference in OS and PFS at12,18,24months between MR4and non-MR4(12months:p=0.034, p=0.001,18months:p=0.013, p<0.001,24months:p=0.007, p<0.001, respectively). No death or progression of disease was observed in patients achieving MR4at12,18,24months at the time of last follow-up. PFS were better in patients achieving MR4at12,18,24months than those achieving CCyR without MMR(CCyR+MMR-)(12months:p=0.013,18months:p=0.007,24months:p=0.005, respectively), but no significant difference in OS. The median interval time from treatment to MR4was12months. Patients with BCR-ABL transcript level≤10%IS at3months after starting IM achieved MR4faster than those not (mean rank62.43vs99.76, p<0.001). Reduced dose IM was not associated with the time to MR4.39(16.5%) met the criterion of Stable MR4. Multivariate analyses showed that low baseline WBC count(OR=0.996, p=0.025), the BCR-ABL transcript level≤10%IS at3months after starting IM(OR=2.132, p=0.088) and MR4at24months (OR=5.698, p<0.001) were independent factors of Stable MR4.Conclusions:The incidences of MR4were8.2%,25.8%,31.3%,35.4%in patients with newly diagnosed CML-CP who received IM at6,12,18,24months after commencing IM respectively. In patients accepted IM within6months of diagnosis, the incidences of MR4at12,18,24months were significantly better than those in patients with an IM interval greater than6months. Reduced dose IM was not associated with the incidence of MR4at specific intervals of treatment. MR4at12,18,24months could predict long-time outcomes. Patients with BCR-ABL transcript level≤10%IS at3months after starting IM achieved MR4faster than those not. Reduced dose IM was not associated with the time to MR4.39(16.5%) patients met the criterion of Stable MR4at the time of last follow-up. Baseline low WBC count, the BCR-ABL transcript level≤10%IS at3months after starting IM and MR4at24months were independent factors of Stable MR4. |
